One of the leading causes of death among humans is cancer. Despite the high mortality rates, many cancers can be cured if detected and treated early. To that end, considerable effort has been devoted to the design and development of screening systems that aid the physician in the detection of the presence of early stage cancerous or precancerous tissue.
One of the more recent methods for detection and treatment of cancers in internal body cavities is fluorescence imaging. This imaging mode provides different information than the conventionally used reflectance imaging mode. In both imaging modes, the physician inserts an endoscope or fiber optic bundle into the body cavity which conducts illumination into the cavity from a light source. In reflectance imaging, the light source is typically white light whereas in fluorescence, a specific excitation wavelength(s) is used. The reflectance or fluorescence image is captured by the imaging fiber bundle of the endoscope and viewed by the physician through the ocular of the endoscope. Alternatively, a camera can be attached to the ocular so that the image can be displayed on a monitor.
In prior art fluorescence imaging systems, a physician typically prepares a patient by administering a photosensitive drug that binds to cancerous tissue. The photosensitive drugs cause the cancerous tissue to contrast with the surrounding tissue, thereby allowing the physician to visually detect the presence of cancer. The problem with the use of photosensitive drugs to detect cancer is that most drugs have significant side effects. The most serious side effect is that the patients become hyper sun sensitive while the drugs are active. Therefore, patients who receive these drugs must be kept in darkened rooms for several days after the administration of the drugs. This method of cancer detection is therefore not suited for screening applications where it is desired to test as many patients as possible in the least amount of time.
Another cancer detection method based on fluorescence imaging that eliminates the need to administer photosensitive drugs is based on the fact that cancerous or precancerous tissue responds differently to applied light than does normal tissue. When monochromatic light is applied to living tissue, a portion of the absorbed light will be re-emitted at different wavelengths in a process termed autofluorescence (also referred to as native fluorescence). If blue or ultraviolet light is applied to living tissue, the intensity or number of autofluorescence photons released by the abnormal tissue in the green portion of the visible light spectrum differs relative to the intensity or number of photons released by healthy tissue. In the red region of the visible light spectrum, the number of photons released by the healthy and abnormal tissue are closer to being similar.
Examples of prior art systems which utilize the difference in fluorescence and autofluorescence intensity to detect the presence of cancer cells include U.S. Pat. No. 4,786,813 to Svanberg et al.; U.S. Pat. No. 4,930,516 ('516) to Alfano et al.; U.S. Pat. No. 5,042,494 ('494) to Alfano; U.K. Patent Application No. 2,203,831, by Zeng Kun; U.S. Pat. No. 5,131,398 ('398) to Alfano et al.; and PCT application No. WZ 90/10219 by Andersson-Engles.
The systems described in each of these patents generally fall into two categories in order to discriminate between cancerous and non-cancerous cells. The first category one utilizes single point, narrow band spectroscopy measurements to detect cancerous tissue, while the second utilizes broad band imaging systems. Examples of the systems in the first category are the Alfano patents, '516, '494 and '398, which describe single point measurement systems. These systems use a ratiometric comparison of the narrow band intensity of autofluorescence light produced by healthy and suspect tissue, as well as a detection of a change in spectral peaks (i.e., a shift towards the blue) to indicate the presence of cancerous cells. However, these narrow band intensity measurements and the associated discrimination algorithm is based on an autofluorescence spectra derived from in vitro measurements of rat tumors that have not been found to be applicable to cancer in humans. The Zeng system simply looks for a change in the spectral envelope of the autofluorescence light to detect malignant tissue. However, this method has not proven sufficiently reliable to identify suspicious tissue in different patients due to changes in the amount of autofluoresence light produced as the probe is moved from one location to another or one patient to another.
Examples of the second category are illustrated by the Svanberg et al. and Andersson-Engles patents, which disclose systems for producing images of diseased tissue. The fluorescence or autofluorescence light produced by the tissue is divided into four beams that are filtered with a broadband filter before being applied to an intensified CCD camera. The output of the intensified CCD camera is used to compute ratios of the intensity of the four broad spectral bands. The ratio calculations are then displayed, typically as pseudo colors, on a monitor so that a physician can visually detect the presence of cancerous lesions. However, the calculation of ratios or the requirement for image processing is not desirable in a medical diagnostic aid system because the physician loses information that is, in our experience, necessary for diagnostic judgment. Such information is only retained by presenting the physician with a view of the tissue directly and not a mathematical representation of the tissue.
A new development which leads to an apparatus for detecting the presence of cancerous tissue based on the differences in autofluorescence light is disclosed in our copending U.S. patent applications Ser. Nos. 08/428,494 ('494), now U.S. Pat. No. 5,507,287 and 08/218,662 ('662), which are herein incorporated by reference. While the systems disclosed in the '494 and '662 applications constitute a significant advance in the field of cancer imaging, improvements can be made. For example, these systems require complex laser systems in order to produce the fluorescence excitation light. Although it is possible to use a relatively small ion laser, such as the HeCd laser, this has the disadvantage that the illumination power is not great enough for the examination of large cavity organs such as the colon and stomach. Furthermore, if fluorescence imaging is used together with white light reflectance imaging, an additional light source has to be used. Additionally, there are currently no cancer imaging systems that are designed to compensate for the changes of autofluorescence properties from patient to patient, from organ to organ, and from location to location. Finally, the manner in which cancerous or precancerous tissue is displayed does not take optimal advantage of the perceived color discrimination of the human eye.
The present invention is directed to address the problems of prior art cancer imaging systems and to improve the systems disclosed in the '494 and '662 applications in order to facilitate the detection of cancerous or precancerous tissue in the respiratory and gastrointestinal tracts.